Disulfiram attenuates morphine or methadone withdrawal syndrome in mice

Taking opioids is often accompanied by the development of dependence. Unfortunately, treatment of opioid dependence is difficult, particularly because of codependence - for example, on alcohol or other drugs of abuse. In the presented study, we analyzed the potential influence of disulfiram, a drug used to aid the management of alcoholism, on opioid abstinence syndrome, which occurs as a result of opioid withdrawal. Opioid dependence in mice was induced by subcutaneous administration of either morphine or methadone at a dose of 48 mg/kg for 10 consecutive days. To trigger a withdrawal syndrome, the opioid receptor antagonist, naloxone, was administered at a dose of 1 mg/kg (subcutaneous), and the severity of withdrawal signs was assessed individually. Interruption of chronic treatment with morphine or methadone by naloxone has led to the occurrence of opioid abstinence signs such as jumping, paw tremor, wet-dog shakes, diarrhea, teeth chattering, ptosis, and piloerection. Importantly, pretreatment with disulfiram (25, 50, and 100 mg/kg) reduced the intensity of withdrawal signs induced by naloxone in morphine or methadone-treated mice. These findings show the effectiveness of disulfiram in reducing opioid abstinence signs.